Thyroid disorders Flashcards
Thyroid gland
A butterfly-shaped gland located in the neck, composed of two lobes connected by an isthmus. It is surrounded by a thin fibrous capsule of connective tissue.
Structure of the thyroid
Thyroid epithelial cells line spaces called follicles, which are filled with colloid, a substance containing thyroid hormones. Parafollicular ‘c’ cells secrete calcitonin. Blood and lymph vessels, nerves and connective tissues are found between follicles.
Function of thyroid hormones
Thyroid hormones are important for:
- control of metabolism
- regulation of growth
- multiple roles in development
Control of thyroid secretion
Secretion of thyroid hormones is controlled by the hypothalamo-pituitary-thyroid axis. The hypothalamus secretes thyrotropin releasing hormone (TRH), stimulating the anterior pituitary to secrete thyroid stimulating hormone (TSH), which stimulates the thyroid to secrete T3 and T4.
Synthesis of thyroid hormones
Thyroid hormones are synthesised in follicular thyroid cells. Iodine is absorbed from the bloodstream and concentrated in follicles, then bound to tyrosine residues on the thyroglobulin precursor molecule by the thyroperoxidase enzyme (TPO). This forms MIT and DIT, which are combined to make the active hormone triiodothyronine (T3) and the prohormone thyroxine (T4).
De-iodination of T4
The biologically active thyroid hormone T3 is produced from the mono-deiodination of the prohormone T4, which is more abundant. Deiodinase enzymes are present in peripheral tissues.
Hormone binding proteins
Thyroid hormones circulate in the bloodstream bound to proteins eg. thyroxine binding globulin (TBG), albumin, transthyretin. Only a very small percentage (T3=0.3%, T4=0.03%) circulates freely.
Tests of thyroid function
- serum TSH
- serum free T3
- serum free T4
Hyperthyroidism
Overactivity of the thyroid gland. Most commonly caused by Graves’ disease, toxic nodular goitre or thyroiditis. May also be caused by exogenous iodine, taking excess thyroid hormone, a TSH secreting pituitary adenoma, or neonatal hyperthyroidism. Prevalence is 10 times greater in females than in males.
Signs and symptoms of hyperthyroidism
- cardiovascular; tachycardia, atrial fibrillation, shortness of breath, ankle swelling
- gastrointestinal; weight loss, diarrhoea, increased appetite
- neurological- tremor, myopathy (muscle weakness), anxiety
- eyes/skin- sore, gritty eyes, diplopia (double vision), staring eyes, pruritus (itching)
Graves’ disease
The most prevalent autoimmune disorder in the UK, constituting 60-80% of cases of hyperthyroidism. Caused by a combination of genetic and environmental factors, with 50% of patients reporting a family history of the condition. Pathogenic antibodies bind to and stimulate TSH receptors on follicular thyroid cells, resulting in the oversecretion of thyroid hormones.
Signs of Graves’ disease
- eyes; lid lag/retraction (staring), conjuctival oedema (swelling), periorbital puffiness, proptosis (bulging), opthalmoplegia (weakness of eye muscles)
- skin; pretibial myxoedema, acropachy
Neonatal hyperthyroidism
Can occur when a mother has Graves’ disease/hyperthyroidism during pregnancy. Pathogenic TSH-R antibodies can cross the placenta, leading to a potentially very dangerous condition for the foetus.
Diagnosis of hyperthyroidism
- low serum TSH
- high free T3 and T4
- clinical features eg. eye signs (50%), diffuse goitre (75-90%)
- thyroperoxidase antibodies (75%)
- TSH receptor antibodies (99%)
- isotope uptake scans using technetium/radioactive iodine
Treatment of hyperthyroidism
- anti-thyroid drugs
- surgery
- radioactive iodine therapy
Thionamides eg. carbimazole (methimazole), propylthiouracil
Anti-thyroid drugs which inhibit thyroperoxidase enzymes, blocking iodine incorporation and organification. Used as a short term solution to prepare patients for other treatment options, or to induce remission in Graves’ disease. Provides rapid control and is generally well tolerated, although side effects may include rashes, joint pains and sickness, as well as the rare incidence of agranulocytosis. Low cure rate (30-40%).
Thyroidectomy
Surgery to remove the whole (total) or part of (partial) the thyroid gland. Complications include hypothyroidism, hypoparathyroidism, damage to the recurrent laryngeal nerve, bleeding, and the sudden release of lots of thyroid hormones into the bloodstream (thyroid storm, less common).
I-131 therapy
Radioactive iodine therapy, in which a fixed dose of radiation is administered to the thyroid gland through a capsule of radioisotope. It is highly effective (85% cure rate), although may worsen eye disease and can carry risks of hypothyroidism, cancer and infertility. It is also contraindicated in pregnancy and breastfeeding.
Hypothyroidism
Underactivity of the thyroid gland. Can be caused by Hashimoto’s thyroiditis, after treatment for hyperthyroidism, subacute/silent thyroiditis, iodine deficiency, and congenital anomalies (thyroid agenesis/ enzyme defects).
Hashimoto’s thyroiditis
The most common cause of hypothyroidism in the UK, involving pathogenic antibodies to thyroperoxidase (TPO) and thyroglobulin (Tg). Causes inflammation of the thyroid and goitre, leading to fibrosis and shrinkage of the thyroid.
Iodine deficiency
A major cause of goitre and hypothyroidism worldwide, particularly prevalent in mountainous and landlocked regions. Supplementation programmes aim to prevent malnutrition.
Signs and symptoms of hypothyroidism
- cardiovascular; bradycardia, heart failure, pericardial effusion
- gastrointestinal; weight gain, constipation
- neurological; depression, psychosis, carpal tunnel syndrome
- skin; myxoedema, erythema ab igne, vitiligo
Treatment of hypothyroidism
Levothyroxine is a drug which can be used to restore patients to a euthyroid state and normalise serum T4 and TSH levels.
Congenital hypothyroidism
Arises when the thryoid fails to develop (agenesis), or when genetic abnormalities lead to enzyme defects. Characterised by cretinism, stunted growth and mental retardation. Newborns are screened using a heel-prick test.
Goitre/thyroid nodules
Enlargement of the thyroid gland, which is extremely prevalent among the population (visible on ultrasound in 50-67%, palpable in 10%). Often found incidentally in patients undergoing imaging.
Investigation of thyroid nodules
- assessment of thyroid function; serum TSH, free T3 and T4
- assessment of thyroid size; imaging (x-ray, CT, MRI), symptoms, respiratory flow loop
- assessment of thyroid pathology; radionuclide scanning, ultrasound, fine needle aspiration cytology
Thyroid cancer
Forms are papillary, follicular, anaplastic and medullary carcinoma. Caused by irradiation, iodine deficiency, oncogene expression and genetic factors. Managed with surgery, radioiodine ablation, thyroxine suppression and measurement of serum thyroglobulin.
Which transporter is responsible for the transport of iodine into thyrocytes?
Na+/I- symporter.
